Switching to unboosted atazanavir improves glucose tolerance in highly pretreated HIV-1 infected subjects

Objective: To evaluate the 24-week effects on glucose tolerance of switching from a protease inhibitor (PI)-based to an unboosted atazanavir-including regimen in highly pretreated HIV-1 infected subjects with metabolic alterations. Design: Prospective, open-label, single-center, 24-week pilot study. Methods: Twenty-one subjects underwent an oral glucose tolerance test (OGTT) at baseline (BL) and after 24 weeks of unboosted atazanavir. Insulin sensitivity and β-cell responsiveness were evaluated on the basis of static and dynamic data; fasting glucose, insulin, C-peptide, triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDI-c), low-density lipoprotein-cholesterol (IDL-c), TC/HDL ratio, CD4+ cell count and HIV-1 RNA were measured. Results: After 24 weeks of unboosted atazanavir, the 120-min glucose level was significantly lower than the one measured at BL (P=0.021); there were no statistically significant differences in the insulin concentration proffie. The SI_oral, an OGTT-based index of insulin sensitivity, was significantly higher at week 24 (P = 0.017); the indices of first- and second-phase β-cell responsiveness did not significantly change. There was no significant difference between BL and 24-week fasting glucose, insulin or C-peptide levels and consequently no change in fasting homeostasis model assessment indices of insulin sensitivity and β-cell function. There were significant improvements in TG (P = 0.009), TC (P = 0.0001), LDL-c (P = 0.019) and TC/HDL-c ratio (P = 0.001), and a similar trend in HDT-c levels (P = 0.069). No significant changes in the immunological and virological parameters were detected. Conclusions: Our results show that switching from a PI-based to an unboosted atazanavir-including regimen leads to a significant improvement in glucose tolerance in highly pretreated HIV-1 infected subjects with metabolic alterations.